JAX
Mouse Strain Datasheet - 005879
D1Lac.Cg-Il4tm1Cgn/J
Also Known As: IL-4 KO
This Il4 knockout strain is useful in studies of arthritis, autoimmunity, and T helper cell immune responses.
Donating Investigator
Linda K Myers, University of Tennessee, Memphis
Genetic overview
| Genetic Background | Generation |
|---|---|
|
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Il4tm1Cgn
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Il4 | interleukin 4 |
Research Applications
- Immunology, Inflammation and Autoimmunity Research
- Cancer Research
Detailed Description
Mice homozygous for the targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. No endogenous gene product is detectable in splenocyte supernatants. Mutant mice crossed to the DBA/1LacJ background (I-Aq haplotype) are susceptible to collagen-induced arthritis. Deletion of the endogenous gene exacerbates both the incidence and severity of collagen-induced arthritis, which is accompanied with increased IgG2 and decreased IgG1 in sera. Following type II collagen (CII) tolerization of mutant mice, splenocytes cultured with CII have increased Th2 (IL-5, IL-9, IL-10, IL-13) and Th1 (IFNgamma, IL-6) cytokines. Mutant mice may be useful in other studies of collagen-induced arthritis, rheumatoid arthritis, mechanisms of tolerance, regulation of autoimmune disease, and T helper cell immune responses.
On the C57BL/6 background (see Stock No. 002253) from which this mouse was created, T and B cell development is normal but IgGl and IgE levels and the ability of homozygous mutant mice to produce Th2-derived cytokines are significantly reduced.
Development
The targeted mutation was generated by disrupting exon 1 of the endogenous gene with a neomycin resistance gene. The construct was electroporated into 129P2/OlaHsd-derived E14-1 embryonic stem cells and the resulting chimeric animals were crossed to C57BL/6 mice for many generations. The mutant mice on DBA/1LacJ background were generated by crossing male B6.129P2-Il4tm1Cgn/J (see Stock No. 002253) with female DBA/1LacJ (see Stock No. 001140) mice for 12 generations before being intercrossed for homozygosity.
Control Suggestions
- Wild-type from the colony
- 001140 DBA/1LacJ
Additional Information
Selected References
- Myers LK; Tang B; Stuart JM; Kang AH. 2002. The role of IL-4 in regulation of murine collagen-induced arthritis. Clin Immunol 102(2):185-91. PubMed: 11846461MGI: J:75149
Il4tm1Cgn
Allele Symbol: Il4tm1Cgn
| Allele Name | targeted mutation 1, University of Cologne |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | IL-4 KO; IL-4-; IL-4KO; IL-4T-; IL4-; IL4tm1cgn129; IL4T |
| Gene Symbol and Name | Il4, interleukin 4 |
| Gene Synonym(s) | BCGF-1; BCGF1; BSF-1; BSF1; IL-4; Il-4; Il-4; Il4e12 |
| Strain of Origin | 129P2/OlaHsd |
| Chromosome | 11 |
| Molecular Note | A translational stop codon and a neomycin resistance gene were inserted into the first exon of the gene. |
| Mutations Made By | Dr. Ralf Kuhn, University of Cologne |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- collagen induced arthritis
- Inflammation
- rheumatoid arthritis
- Autoimmunity
Genotype: Il4tm1Cgn related
- Cancer Research
- Growth Factors/Receptors/Cytokines
- Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
Mammalian Phenotype Terms by Genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Il4tm1Cgn/Il4tm1Cgn
B6.Cg-Il4tm1Cgn
immune system phenotype
- abnormal T-helper 2 physiology
- abnormal humoral immune response
- IgG1 response to immunization with the protein antigen OVA is severely impaired (MGI Ref ID J:89095)
hematopoietic system phenotype
Genotype: Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * NOD
immune system phenotype
- abnormal cytokine secretion
- CD4+ T cells from deficient animals show a strongly reduced ability to produce Il5 after anti-TCR stimulation compared to wild-type cells (MGI Ref ID J:85924)
- decreased IgG1 level
- CD4+ T cells from deficient animals show a reduction in circulating IgG1 in the absence of deliberate immunization (MGI Ref ID J:85924)
hematopoietic system phenotype
- decreased IgG1 level
- CD4+ T cells from deficient animals show a reduction in circulating IgG1 in the absence of deliberate immunization (MGI Ref ID J:85924)
Genotype: Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * C57BL/6
immune system phenotype
- abnormal cytokine secretion
- conA stimulated spleen cells from homozygotes secrete ~800-fold less Il4 than control cells (MGI Ref ID J:704)
- decreased IgE level
- after infection with a nematode, 6-week old animals have almost undetectable IgE levels compared to controls which show about 50-fold increase in levels after infection (MGI Ref ID J:704)
- there were no dectectable levels of IgE in 5 of 6 mice compared to controls, which all had dectectable levels (MGI Ref ID J:704)
- decreased IgG1 level
- granulomatous inflammation
hematopoietic system phenotype
- decreased IgE level
- after infection with a nematode, 6-week old animals have almost undetectable IgE levels compared to controls which show about 50-fold increase in levels after infection (MGI Ref ID J:704)
- there were no dectectable levels of IgE in 5 of 6 mice compared to controls, which all had dectectable levels (MGI Ref ID J:704)
Genotype: Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * A/WySn * C57BL/10SnSg * Swiss
homeostasis/metabolism phenotype
- abnormal physiological response to xenobiotic
immune system phenotype
- decreased IgG1 level
- following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice (MGI Ref ID J:119207)
- increased IgG2a level
- following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice (MGI Ref ID J:119207)
hematopoietic system phenotype
- decreased IgG1 level
- following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice (MGI Ref ID J:119207)
- increased IgG2a level
- following exposure to HgCl2 for 4 weeks, relative to similarly treated wild-type and heterozygous mice (MGI Ref ID J:119207)
Genotype: Il4tm1Cgn/Il4tm1Cgn
involves: 129P2/OlaHsd * C57BL/6J * MRL/Mp
immune system phenotype
- decreased IgE level
- at 3 months of age relative to wild-type controls (MGI Ref ID J:39600)
- decreased IgG1 level
- at 3 and 7-8 months of age relative to wild-type controls (MGI Ref ID J:39600)
hematopoietic system phenotype
- decreased IgE level
- at 3 months of age relative to wild-type controls (MGI Ref ID J:39600)
- decreased IgG1 level
- at 3 and 7-8 months of age relative to wild-type controls (MGI Ref ID J:39600)
Genotype: Il4tm1Cgn/Il4tm1Cgn
B6.129P2-Il4tm1Cgn/J
immune system phenotype
- immune system phenotype
integument phenotype
- abnormal skin physiology
- despite normal dendritic function, mice whose backs are shaved and painted with Alexa 647-labeled ovalbumin accumulate fewer Alexa647+CD11c+ cells in draining lymph nodes compared with similarly treated wild-type mice indicating increased barrier function (MGI Ref ID J:160119)
Genotype: Il4tm1Cgn/Il4tm1Cgn
MRL.129P2-Il4tm1Cgn
immune system phenotype
- lacrimal gland inflammation
- B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice (MGI Ref ID J:132514)
- dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells (MGI Ref ID J:132514)
- predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate (MGI Ref ID J:132514)
vision/eye phenotype
- lacrimal gland inflammation
- B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice (MGI Ref ID J:132514)
- dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells (MGI Ref ID J:132514)
- predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate (MGI Ref ID J:132514)
endocrine/exocrine gland phenotype
- lacrimal gland inflammation
- B cells are more abundant in infiltrates (30%) than in MRL.Cg- Il4tm1Cgn Faslpr mice (MGI Ref ID J:132514)
- dacryoadenitis, characterized by multiple foci of mononuclear inflammatory cells (MGI Ref ID J:132514)
- predominant cell type in infiltrate at various ages is CD4+ T cells (66%); CD8+ T cells make up 12% of infiltrate (MGI Ref ID J:132514)
References
- Myers LK; Tang B; Stuart JM; Kang AH. 2002. The role of IL-4 in regulation of murine collagen-induced arthritis. Clin Immunol 102(2):185-91. PubMed: 11846461MGI: J:75149
Additional - Il4tm1Cgn related
- Aguirre SA; Perryman LE; Davis WC; McGuire TC. 1998. IL-4 protects adult C57BL/6 mice from prolonged Cryptosporidium parvum infection: analysis of CD4+alpha beta+IFN-gamma+ and CD4+alpha beta+IL-4+ lymphocytes in gut-associated lymphoid tissue during resolution of infection. J Immunol 161(4):1891-900. PubMed: 9712058MGI: J:49699
- Alard P; Clark SL; Kosiewicz MM. 2004. Mechanisms of tolerance induced by TGF beta-treated APC: CD4 regulatory T cells prevent the induction of the immune response possibly through a mechanism involving TGF beta. Eur J Immunol 34(4):1021-30. PubMed: 15048712MGI: J:115475
- Andersen C; Jensen T; Nansen A; Marker O; Thomsen AR. 1999. CD4(+) T cell-mediated protection against a lethal outcome of systemic infection with vesicular stomatitis virus requires CD40 ligand expression, but not IFN-gamma or IL-4. Int Immunol 11(12):2035-42. PubMed: 10590269MGI: J:110491
- Anderson AC; Reddy J; Nazareno R; Sobel RA; Nicholson LB; Kuchroo VK. 2004. IL-10 plays an important role in the homeostatic regulation of the autoreactive repertoire in naive mice. J Immunol 173(2):828-34. PubMed: 15240669MGI: J:91913
- Araujo-Pires AC; Vieira AE; Francisconi CF; Biguetti CC; Glowacki A; Yoshizawa S; Campanelli AP; Trombone AP; Sfeir CS; Little SR; Garlet GP. 2015. IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis. J Bone Miner Res 30(3):412-22. PubMed: 25264308MGI: J:233363
- Babayan SA; Read AF; Lawrence RA; Bain O; Allen JE. 2010. Filarial parasites develop faster and reproduce earlier in response to host immune effectors that determine filarial life expectancy. PLoS Biol 8(10):e1000525. PubMed: 20976099MGI: J:167364
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- Bancroft AJ; McKenzie AN; Grencis RK. 1998. A critical role for IL-13 in resistance to intestinal nematode infection. J Immunol 160(7):3453-61. PubMed: 9531306MGI: J:111618
- Beal AM; Ramos-Hernandez N; Riling CR; Nowelsky EA; Oliver PM. 2011. TGF-beta induces the expression of the adaptor Ndfip1 to silence IL-4 production during iT(reg) cell differentiation. Nat Immunol 13(1):77-85. PubMed: 22080920MGI: J:179003
- Bediako Y; Bian Y; Zhang H; Cho H; Stein PL; Wang CR. 2012. SAP is required for the development of innate phenotype in H2-M3--restricted Cd8(+) T cells. J Immunol 189(10):4787-96. PubMed: 23041566MGI: J:190592
- Beenhouwer DO; Shapiro S; Feldmesser M; Casadevall A; Scharff MD. 2001. Both Th1 and Th2 Cytokines Affect the Ability of Monoclonal Antibodies To Protect Mice against Cryptococcus neoformans. Infect Immun 69(10):6445-55. PubMed: 11553589MGI: J:71570
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- Blackstock R; Murphy JW. 2004. Role of interleukin-4 in resistance to Cryptococcus neoformans infection. Am J Respir Cell Mol Biol 30(1):109-17. PubMed: 12855407MGI: J:95350
- Bour-Jordan H; Thompson HL; Bluestone JA. 2005. Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice. J Immunol 175(9):5649-55. PubMed: 16237054MGI: J:119359
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- D'Orazio TJ; Niederkorn JY. 1998. A novel role for TGF-beta and IL-10 in the induction of immune privilege. J Immunol 160(5):2089-98. PubMed: 9498745MGI: J:111362
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- Denzel A; Maus UA; Rodriguez Gomez M; Moll C; Niedermeier M; Winter C; Maus R; Hollingshead S; Briles DE; Kunz-Schughart LA; Talke Y; Mack M. 2008. Basophils enhance immunological memory responses. Nat Immunol 9(7):733-42. PubMed: 18516038MGI: J:137679
- Derecki NC; Cardani AN; Yang CH; Quinnies KM; Crihfield A; Lynch KR; Kipnis J. 2010. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 207(5):1067-80. PubMed: 20439540MGI: J:160932
- Diaz-de-Durana Y; Mantchev GT; Bram RJ; Franco A. 2006. TACI-BLyS signaling via B-cell-dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo. Blood 107(2):594-601. PubMed: 16195331MGI: J:126637
- Dieli F; Sireci G; Scire E; Salerno A; Bellavia A. 1999. Impaired contact hypersensitivity to trinitrochlorobenzene in interleukin-4-deficient mice. Immunology 98(1):71-9. PubMed: 10469236MGI: J:110461
- Dohi T; Fujihashi K; Koga T; Etani Y; Yoshino N; Kawamura YI; McGhee JR. 2004. CD4+CD45RBHi interleukin-4 defective T cells elicit antral gastritis and duodenitis. Am J Pathol 165(4):1257-68. PubMed: 15466391MGI: J:93676
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- Everest P; Allen J; Papakonstantinopoulou A; Mastroeni P; Roberts M ; Dougan G. 1997. Salmonella typhimurium infections in mice deficient in interleukin-4 production: role of IL-4 in infection-associated pathology. J Immunol 159(4):1820-7. PubMed: 9257845MGI: J:42104
- Fallon PG; Ballantyne SJ; Mangan NE; Barlow JL; Dasvarma A; Hewett DR; McIlgorm A; Jolin HE; McKenzie AN. 2006. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med 203(4):1105-16. PubMed: 16606668MGI: J:123748
- Fallon PG; Emson CL; Smith P; McKenzie AN. 2001. IL-13 overexpression predisposes to anaphylaxis following antigen sensitization. J Immunol 166(4):2712-6. PubMed: 11160336MGI: J:135014
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- Fousteri G; Dave A; Bot A; Juntti T; Omid S; von Herrath M. 2010. Subcutaneous insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFNgamma. Diabetologia 53(9):1958-70. PubMed: 20490452MGI: J:163357
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- Hao J; Dong S; Xia S; He W; Jia H; Zhang S; Wei J; O'Brien RL; Born WK; Wu Z; Wang P; Han J; Hong Z; Zhao L; Yin Z. 2011. Regulatory role of Vgamma1 gammadelta T cells in tumor immunity through IL-4 production. J Immunol 187(10):4979-86. PubMed: 21987661MGI: J:179639
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- Hasnain SZ; Evans CM; Roy M; Gallagher AL; Kindrachuk KN; Barron L; Dickey BF; Wilson MS; Wynn TA; Grencis RK; Thornton DJ. 2011. Muc5ac: a critical component mediating the rejection of enteric nematodes. J Exp Med 208(5):893-900. PubMed: 21502330MGI: J:177306
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- Havarinasab S; Pollard KM; Hultman P. 2009. Gold- and silver-induced murine autoimmunity--requirement for cytokines and CD28 in murine heavy metal-induced autoimmunity. Clin Exp Immunol 155(3):567-76. PubMed: 19077085MGI: J:146057
- Hertz CJ; Filutowicz H; Mansfield JM. 1998. Resistance to the African trypanosomes is IFN-gamma dependent. J Immunol 161(12):6775-83. PubMed: 9862708MGI: J:115095
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- Hofstetter HH; Sewell DL; Liu F; Sandor M; Forsthuber T; Lehmann PV; Fabry Z. 2003. Autoreactive T cells promote post-traumatic healing in the central nervous system. J Neuroimmunol 134(1-2):25-34. PubMed: 12507769MGI: J:119263
- Horsley V; Jansen KM; Mills ST; Pavlath GK. 2003. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell 113(4):483-94. PubMed: 12757709MGI: J:107688
- Hoving JC; Nieuwenhuizen NE; Schafer G; Katz AA; Brombacher F. 2016. IL-13 Signals Independent of IL-4 Receptor-Alpha Chain to Drive Ovalbumin-Induced Dermatitis. J Invest Dermatol 136(6):1286-90. PubMed: 26896776MGI: J:233456
- Huaux F; Liu T; McGarry B; Ullenbruch M; Phan SH. 2003. Dual roles of IL-4 in lung injury and fibrosis. J Immunol 170(4):2083-92. PubMed: 12574379MGI: J:126708
- Hubner MP; Shi Y; Torrero MN; Mueller E; Larson D; Soloviova K; Gondorf F; Hoerauf A; Killoran KE; Stocker JT; Davies SJ; Tarbell KV; Mitre E. 2012. Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-beta. J Immunol 188(2):559-68. PubMed: 22174447MGI: J:180789
- Hung K; Hayashi R; Lafond-Walker A; Lowenstein C; Pardoll D; Levitsky H. 1998. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 188(12):2357-68. PubMed: 9858522MGI: J:51677
- Inoue Y; Konieczny BT; Wagener ME; McKenzie AN; Lakkis FG. 2001. Failure to induce neonatal tolerance in mice that lack both IL-4 and IL-13 but not in those that lack IL-4 alone. J Immunol 167(2):1125-8. PubMed: 11441125MGI: J:106687
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